{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T05:07:14Z","timestamp":1793855234792,"version":"4.6.1"},"reference-count":175,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2019,10,29]],"date-time":"2019-10-29T00:00:00Z","timestamp":1572307200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010661","name":"Horizon 2020","doi-asserted-by":"publisher","award":["Marie Sklodowska-Curie ITN-TREATMENT Grant Agreement 721236"],"award-info":[{"award-number":["Marie Sklodowska-Curie ITN-TREATMENT Grant Agreement 721236"]}],"id":[{"id":"10.13039\/100010661","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014440","name":"Ministerio de Ciencia, Innovaci\u00f3n y Universidades","doi-asserted-by":"publisher","award":["RTI2018-094052-B MICINN\/FEDER"],"award-info":[{"award-number":["RTI2018-094052-B MICINN\/FEDER"]}],"id":[{"id":"10.13039\/100014440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012818","name":"Comunidad de Madrid","doi-asserted-by":"publisher","award":["S2017\/BMD-3684 MOIR2-CM"],"award-info":[{"award-number":["S2017\/BMD-3684 MOIR2-CM"]}],"id":[{"id":"10.13039\/100012818","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Centro de Investigacion Biomedica en Red de Diabetes y Enfermedades Metabolicas Asociadas","award":["CIBERDEM"],"award-info":[{"award-number":["CIBERDEM"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Second-generation antipsychotics (SGAs) are the cornerstone of treatment for schizophrenia because of their high clinical efficacy. However, SGA treatment is associated with severe metabolic alterations and body weight gain, which can increase the risk of type 2 diabetes and cardiovascular disease, and greatly accelerate mortality. Several underlying mechanisms have been proposed for antipsychotic-induced weight gain (AIWG), but some studies suggest that metabolic changes in insulin-sensitive tissues can be triggered before the onset of AIWG. In this review, we give an outlook on current research about the metabolic disturbances provoked by SGAs, with a particular focus on whole-body glucose homeostasis disturbances induced independently of AIWG, lipid dysregulation or adipose tissue disturbances. Specifically, we discuss the mechanistic insights gleamed from cellular and preclinical animal studies that have reported on the impact of SGAs on insulin signaling, endogenous glucose production, glucose uptake and insulin secretion in the liver, skeletal muscle and the endocrine pancreas. Finally, we discuss some of the genetic and epigenetic changes that might explain the different susceptibilities of SGA-treated patients to the metabolic side-effects of antipsychotics.<\/jats:p>","DOI":"10.3390\/cells8111336","type":"journal-article","created":{"date-parts":[[2019,10,31]],"date-time":"2019-10-31T05:18:26Z","timestamp":1572499106000},"page":"1336","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":170,"title":["Second-Generation Antipsychotics and Dysregulation of Glucose Metabolism: Beyond Weight Gain"],"prefix":"10.3390","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9332-6979","authenticated-orcid":false,"given":"Diana","family":"Grajales","sequence":"first","affiliation":[{"name":"Instituto de Investigaciones Biom\u00e9dicas Alberto Sols (CSIC-UAM), 28029 Madrid, Spain"},{"name":"CIBER de Diabetes y Enfermedades Metab\u00f3licas Asociadas (CIBERDEM), ISCIII, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vitor","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Biom\u00e9dicas Alberto Sols (CSIC-UAM), 28029 Madrid, Spain"},{"name":"CIBER de Diabetes y Enfermedades Metab\u00f3licas Asociadas (CIBERDEM), ISCIII, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c1ngela M.","family":"Valverde","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Biom\u00e9dicas Alberto Sols (CSIC-UAM), 28029 Madrid, Spain"},{"name":"CIBER de Diabetes y Enfermedades Metab\u00f3licas Asociadas (CIBERDEM), ISCIII, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,10,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3280","DOI":"10.2174\/1381612821666150619092903","article-title":"Off-Label Prescribing of Antipsychotics in Adults, Children and Elderly Individuals: A Systematic Review of Recent Prescription Trends","volume":"21","author":"Carton","year":"2015","journal-title":"Curr. 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